Natural killer (NK) cells are important components of the immune system because of their ability to directly kill pathogen-infected and tumor cells, as well as their immunoregulatory functions via production of pro-inflammatory cytokines and chemokines. During maturation, NK cells acquire cytokine receptors, activating and inhibitory receptors, adhesion molecules and NK cell effectors functions. In mouse, the committed NK cell precursors (NKP) express the common gamma chain receptor (R) for IL-2 and IL-15 (CD122), IL-7Rα (CD127), and c-kit (CD117). NK cell precursors then acquire an immature phenotype in C57BL/6 mice with the acquisition of NK1.1, CD94, the TNFR superfamily member CD27, the integrin CD11b and Ly49 receptors. Additionally, during terminal maturation, NK cells down modulate CD27 and acquire high surface density expression of CD11b.
Acquisition of lytic functions and interferon-gamma (IFN-γ) production in NK cells depends on complex interactions that involve signaling molecules, transcription factors, and microRNAs (MiRs). MiRs are small non-coding RNA that modulate post-transcriptional gene expression of multiple targets, and are implicated in regulating several cellular and developmental processes. MiRs regulate gene expression by binding to the 3′ UTR and inducing either suppression of mRNA translation or mRNA degradation.
In spite of considerable research into therapies to treat these diseases, they remain difficult to treat effectively, and the mortality observed in patients indicates that improvements are needed in the diagnosis, treatment, and prevention of these diseases.
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